It is known that certain histamine H.sub.2 -receptor antagonists are effective in treating gastric disorders such as peptic and gastric ulcers. Familiar compounds of this type are cimetidine, ranitidine and famotidine.
The compound 3-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methtyl]thio]-N-(aminosulfony l)propanimidamide ("famotidine") is an effective anti-ulcerative of this class.
Sucralfate is a complex of sulfated sucrose and aluminum hydroxide which acts as an anti-ulcerative by forming a cytoprotective barrier at the ulcer site. The drug is administered orally, and has been found useful in treatment of gastric and duodenal ulcers. See, W. A. Ritschel, Antacids and Other Drugs in GI Diseases, Drug Intelligence Publications: Hamilton, Ill. (1984).
It has been proposed to administer sucralfate in combination with histamine H.sub.2 -receptor antagonists. For example, published application WO 92/09286 discloses pharmaceutical compositions which contain a histamine H.sub.2 -receptor antagonist (such as famotidine) in combination with sucralfate, in which compositions the sucralfate acts as a bioadhesive and buffer. It is disclosed that the histamine H.sub.2 -receptor antagonist and the sucralfate form a bioadhesive complex in vivo, which targets the antagonist to the stomach wall. The disclosed compositions may be prepared in the form of powders, tablets or liquid suspensions.
When famotidine and sucralfate are administered together, the sucralfate acts to neutralize stomach acidity while famotidine acts to inhibit acid secretion, and the combined action is very effective.
While compositions containing famotidine and sucralfate are quite effective in treating gastric disorders, it has been found that, in compositions which contain both famotidine and sucralfate in combination, the sucralfate tends to degrade the famotidine, making the compositions less efficacious.